Biased usage of BV gene families of T-cell receptors of WT1 (Wilms' tumor gene)-specific CD8+ T cells in patients with myeloid malignancies
Biased usage of BV gene families of T-cell receptors of WT1 (Wilms' tumor gene)-specific CD8+ T cells in patients with myeloid malignancies
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DOI：
10.1111/j.1349-7006.2009.01453.x
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发表时间：
2010-03-01
期刊：
影响因子：
5.7
通讯作者：
Sugiyama, Haruo
中科院分区：
文献类型：
--
作者：
Tanaka-Harada, Yukie;Kawakami, Manabu;Sugiyama, Haruo
WT 1（Wilms' tumor gene 1）蛋白是一种有效的泛肿瘤相关抗原（TAA），并且在急性髓性白血病（AML）或骨髓增生异常综合征（MDS）患者中自发诱导WT 1特异性细胞毒性T淋巴细胞（WT 1四聚体（+）CD 8（+）T细胞）。我们对HLA-A*2402（+）AML或MDS患者和健康供体（HD）中共计1242个自发诱导的WT 1四聚体（+）CD 8（+）T细胞的T细胞受体β链可变区（TCR-BV）基因家族进行了单细胞水平比较分析。这是首次在单细胞水平上对TAA特异性CD 8（+）T细胞的TCR-BV基因家族进行直接使用分析。使用单个FACS分选的WT 1四聚体（+）CD 8（+）T细胞的TCR-BV基因家族的单细胞RT-PCR进行的使用分析首次显示：（i）BV 5、6、20和27在HD和患者中普遍存在偏倚;（ii）BV 4在HD和MDS患者中普遍存在偏倚;（iii）BV 19在患者中普遍存在偏倚; BV 7和28、BV 9和15以及BV 12和29分别在HD、AML和MDS患者中特异性偏倚。然而，对HD、AML和MDS中24种TCR-BV基因家族的个体使用频率的相似性进行统计分析表明，AML和MDS患者中TCR-BV基因家族的使用频率反映了HD中的使用频率。这些发现为更好地理解WT 1特异性免疫反应提供了新的见解。（Cancer Sci 2010; 101：594-600）
WT1 (Wilms' tumor gene 1) protein is a potent pan-tumor-associated antigen (TAA) and WT1-specific cytotoxic T lymphocytes (WT1 tetramer(+) CD8(+) T cells) are spontaneously induced in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We conducted a single-cell level comparative analysis of T-cell receptor beta-chain variable region (TCR-BV) gene families of a total of 1242 spontaneously induced WT1 tetramer(+) CD8(+) T cells in HLA-A*2402(+) patients with AML or MDS and those in healthy donors (HDs). This is the first report of direct usage analysis of TCR-BV gene families of individual TAA-specific CD8(+) T cells at single-cell level. Usage analysis using single-cell RT-PCR of TCR-BV gene families of individual FACS-sorted WT1 tetramer(+) CD8(+) T cells showed for the first time (i) that BVs 5, 6, 20, and 27 were commonly biased in both HDs and patients; (ii) that BV4 was commonly biased in HDs and MDS patients; (iii) that BV19 was commonly biased in the patients; and (iv) that BVs 7 and 28, BVs 9 and 15, and BVs 12 and 29 were specifically biased in HDs, AML, and MDS patients, respectively. However, statistical analysis of similarity among HD, AML, and MDS of individual usage frequencies of 24 kinds of TCR-BV gene families indicated that the usage frequencies of TCR-BV gene families in AML and MDS patients reflect those in HDs. These findings represent a novel insight for a better understanding of WT1-specific immune response. (Cancer Sci 2010; 101: 594-600)